Adverse effects of growth hormone replacement therapy in children

Abstract

SUMMARYHuman growth hormone (hGH) replacement therapy has been widely available for clinical purposes for more than fifty years. Starting in 1958, hGH was obtained from cadaveric pituitaries, but in 1985 the association between hGH therapy and Creutzfeldt-Jakob disease was reported. In the same year, the use of recombinant hGH (rhGH) was approved. Side effects of rhGH replacement therapy in children and adolescents include rash and pain at injection site, transient fever, prepubertal gynecomastia, arthralgia, edema, benign intracranial hypertension, insulin resistance, progression of scoliosis, and slipped capital femoral epiphysis. Since GH stimulates cell multiplication, development of neoplasms is a concern. We will review the side effects reported in all rhGH indications. Arq Bras Endocrinol Metab. 2011;55(8):559-65 Keywords Growth hormone; side effects; gynecomastia; intracranial hypertension; scoliosis; pediatrics; short stature SUMáRio A terapia de reposição de hormônio de crescimento (hGH) tem sido amplamente disponível para uso clínico por mais de 50 anos. Inicialmente, em 1958, hGH era obtido de hipófises de cadáveres, mas em 1985 foi relatada a associação entre terapia com hGH e doença de Creutzfeldt--Jakob. No mesmo ano o uso de hGH recombinante (rhGH) foi aprovado. Os efeitos adversos que crianças e adolescentes em terapia de reposição de rhGH podem apresentar incluem erupção cutânea e dor no local da aplicação, febre transitória, ginecomastia pré-puberal, artralgia, edema, hipertensão intracraniana benigna, resistência insulínica, progressão de escoliose e epifisiólise da cabeça do fêmur. Como o GH estimula a multiplicação celular, o desenvolvimento de neoplasias é uma preocupação. Neste artigo, revisaremos os possíveis efeitos adversos do rhGH em cada uma de suas indicações clínicas. Arq Bras Endocrinol Metab. 2011;55(8):559-65 Descritores Hormônio do crescimento; efeitos adversos; ginecomastia; hipertensão intracraniana; escoliose; pediatria; baixa estatura review

Elevated serum IGF‐I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia

“…This difference remained statistically significant even after additional controlling for pubertal stages (both P < 0·005). Both GH‐ and IGF‐I receptors are present in human as well as in animal breast tissue, and several studies have established the important role of both hormones in normal development of mammary tissue and the development of gynaecomastia is a known adverse effect in boys and men in human GH replacement therapy …”

“…In addition to its well‐known stimulatory effects on linear growth, GH also acts via its receptor in multiple tissues including liver, fat tissue, gonads and breast tissue. In fact, gynaecomastia is a known side effect during GH therapy …”

“…In fact, gynaecomastia is a known side effect during GH therapy. 13,15 The aim of this study was to evaluate the relationship between pubertal gynaecomastia and sex steroid levels, insulin-like growth factor I (IGF-I), prolactin and body composition.…”

Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation: Erratum.

“…We next determined if our transient, low dose GH therapy produced any of the known side effects of prolonged GH therapy in our mouse model of cutaneous inflammation such as altered body weight, temperature or induction of hyperglycemia [6,60,63]. We found that the highest dose (0.5mg/kg ip.…”

Reversible brain lesion following growth hormone replacement therapy in an adolescent

“…Several acute and long-term side effects may be related to the use of rhGH such as headache, rash, pain at injection site, transient fever, idiopathic intracranial hypertension, pseudotumour cerebri, increased intraocular pressure, slipped upper femoral epiphysis and deterioration of existing scoliosis 6. A recent position paper concerning the safety of rhGH derived from the Endocrine Society, Pediatric Endocrine Society and Growth Hormone Research Society concluded that growth hormone (GH) continues to have a good safety record when used for approved indications and at the recommended doses.…”